1

Question 1

The clonal selection hypothesis states that lymphocytes specific for a large number of different determinants exist prior to antigen exposure. Each specificity is represented by only a small number of cells and antigen exposure leads to expansion of clones specific for the antigen. Which of the following experimental findings would most strongly support the clonal selection hypothesis?

A The total number of lymphocytes increases during an infection.

B Single-cell DNA sequencing demonstrates that a large proportion of naïve lymphocytes share the same antigen receptor sequence.

C Each lymphocyte clone can recognise a vast array of different antigens.

D As a T cell clone expands following antigen exposure, their receptors change and are able to recognise many other different antigens.

E Proliferating daughter lymphocytes express receptors with the same sequence as those of the antigen-exposed parent cell.

Answer 1

E

M1; 1

Question 2

Which of the following statements refers to an innate immune response?

A A large number of naïve lymphocyte clones continuously circulate around the body seeking their cognate antigen.

B In a patient with an autoimmune disease, B cells produce antibodies that can bind to self-antigens.

C T and B cells rearrange their antigen receptors during development.

D Patients vaccinated against a virus are more likely to be protected compared to unvaccinated patients.

E In the lung, the airway epithelial cells produce anti-microbial peptides to prevent infection by pathogens.

Answer 2

E

M1; 2

Question 3

Which of the following statements best describes events during an adaptive immune response?

A Phagocytes produce cytokines to attract lymphocytes to the site of inflammation.

B Exposure of dendritic cells to pathogen associated molecular patterns (PAMPS) increases their antigen processing and presentation abilities.

C During an inflammatory response, endothelial cells express adhesion molecules for leukocytes to roll and migrate into the inflamed tissue.

D Activated T cells expand and then kill infected cells.

E Complement opsonises microbes resulting in their lysis.

Answer 3

D

M1; 3

Question 4

AIRE expressed by medullary thymic epithelial cells permits expression of a wide variety of otherwise tissue-specific peptides. How does this process maintain self-tolerance?

A It permits a broad range of self-peptides to be presented by MHC molecules. T cells that react to these self-antigens presented by medullary thymic epithelial cells are deleted.

B Tissue-specific peptides block binding of the TCR to self-MHC molecules, preventing activation of autoreactive T cells.

C Expression of AIRE downregulates expression of co-stimulatory molecules, which can “over” activate T cells to become autoreactive.

D Expression of AIRE upregulates expression of co-inhibitory molecules, which can instruct T cells to maintain tolerance.

E Expression of AIRE converts thymocytes into regulatory T cells.

Answer 4

A

M1; 4

Question 5

Regarding peripheral lymphoid organs, which of the following statement is correct?

A B cells and T cells occupy separate zones. This segregation is maintained by a hormone gradient.

B Stromal cells (non-APC’s) can present antigens and activate naïve lymphocytes.

C The lymph nodes are the major site of immune responses to blood borne antigens.

D High endothelial venules allow lymphocytes circulating in the blood to migrate into the lymph node.

E The thymus is a peripheral lymphoid organ where T cells undergo maturation.

Answer 5

D

M1; 5

Question 6

Affinity maturation, isotype switching and memory cell generation are important processes for B cells to mount an adequate immune response during an infection. Where do these important processes occur?

A The site of infection

B Central medulla (thymus)

C Germinal centres

D Bone marrow

E Red pulp (spleen)

Answer 6

C

M1; 6

Question 7

MHC class I and class II molecules present peptides on the cell surface for recognition by antigen-specific T lymphocytes. Which of the following statements is true of MHC molecules?

A MHC class I molecules are recognised by CD4+ T cells and MHC class II molecules are recognised by CD8+ T cells.

B MHC class I and class II molecules present polysaccharide antigens for recognition by B cells.

C MHC class II is expressed by all nucleated cells.

D When peptides bind to MHC molecules, anchor residues of the peptide interact with the pockets in the floor of the peptide binding groove.

E Expression of MHC genes is downregulated by interferon-y.

Answer 7

D

M1; 7

Question 8

Typically, MHC class I molecules present peptides derived from intracellular proteins and MHC class II molecules present peptides derived from extracellular proteins. Cross-presentation of peptides requires alternative antigen process pathways to bypass the ‘typical’ pathways. Which of the following pathways allows peptides derived from intracellular proteins to be presented by MHC class II molecules?

A TAP1 mediated transport of peptides into the endoplasmic reticulum.

B Autophagy-mediated antigen processing.

C Endocytosis of extracellular proteins.

D Ubiquitination of intracellular proteins.

E T cell activation.

Answer 8

B

M1; 8

Question 9

Regarding HLA/MHC polymorphism, which of the following statements is true?

A HLA/MHC polymorphism influences which peptides are presented by a particular allomorph.

B HLA/MHC polymorphism arises mainly from somatic V(D)J recombination.

C HLA/MHC allele diversity profile is similar across different ethnic groups.

D HLA/MHC polymorphism is a major reason why organ transplantation between genetically dissimilar individuals is feasible.

E HLA/MHC polymorphism renders a population more vulnerable to a pandemic.

Answer 9

A

M1; 9

Question 10

Positive selection is a process where the TCR repertoire is shaped to promote recognition of self-MHC plus foreign antigenic peptide. However, foreign peptides are not available in the thymus under normal conditions. How does positive selection generate T cells that can recognise foreign peptides?

A Positive selection removes any T cells that recognise self-peptide/self-MHC complexes with high affinity.

B AIRE expressed by medullary thymic epithelial cells permits expression of a wide variety of peptides, including foreign peptides.

C Positive selection generates T cells that receive low affinity signals from self-peptide/self-MHC complexes and these T cells are poised to be activated upon foreign peptide recognition in the periphery.

D During an infection, dendritic cells capture foreign antigens, migrate to the thymus and present foreign peptides to immature T cells undergoing positive selection.

E All TCRs have a high affinity towards foreign peptides.

Answer 10

C

M1; 10

Question 11

What is the primary ‘peripheral regulation’ mechanism that prevents autoimmunity?

A Positive and negative selection in the thymus

B Generation of regulatory T cells.

C Downregulation of co-stimulatory molecules.

D CTLA-4 expression by professional antigen presenting cells (APCs).

E AIRE expression regulated by stromal cells in the peripheral lymphoid organs.

Answer 11

B

M1; 11

Question 12

During T cell development, pre-T cells are double positive for both CD4 and CD8 co-receptors. Double positive cells undergo positive selection and they downregulate either CD4 or CD8 co-receptors to become single positive T cells. Which of the following statements best describes how a give co-receptor is chosen for downregulation?

A TCR specificity for either MHC class I or class II molecules correlates with downregulation of CD4 or CD8, respectively.

B T lymphocytes downregulate CD4 after commitment to cytotoxic effector function.

C Double positive cells determine which co-receptor will be downregulated depending on which survival cytokine they receive during positive selection.

D TCR with an intermediate affinity towards self-peptide self-MHC complexes will down-regulate CD8 in order to become CD4+ regulatory T cells. The rest will become CD8+ T cells.

E Somatic V(D)J recombination determines whether TCR should non-covalently associate with CD4 or CD8 co-receptors.

Answer 12

A

M1; 12

Question 13

T-independent antigens trigger antibody secretion by activated B cells without receiving help from T cells. Which of the following statements is correct about B cell activation in response to T-independent antigens?

A Bacterial surface proteins elicit this response.

B The main isotype class of antibody secreted by this response is IgG.

C Mucosal T-independent antigens will elicit B cells to produce IgA antibodies.

D ABO blood group antigens are examples of T-independent antigens.

E B cell activation by T-independent antigens occurs primarily in the follicles of peripheral lymphoid organs.

Answer 13

D

M1; 13

Question 14

T-dependent antigens trigger CD4+ T cells to provide “help” to B cells in order to elicit more efficient antibody production. Which of the following ligand-receptor pairs is required for this process?

A CD40 & CD40L

B Lipopolysaccharide (LPS) & TLR4

C CTLA4 & CD86

D PD1 & PDL-1

E IL-1 & IL-1R.

Answer 14

A

M1; 14

Question 15

Which of the following is NOT a property of chemokines?

A Chemokines belong to the family of cytokines.

B Chemokines direct migration of leukocytes to a site of inflammation.

C An increased chemokine concentration level in the serum is required to direct leukocytes to a particular site.

D Chemokine receptor expression is cell-type specific and differs between resting and activated cell types.

E Chemokines are produced by many cell types.

Answer 15

C

M1; 15

Question 16

During a viral infection, a novel molecule ‘X’ is found to be secreted by granulocytes and stromal cells in the peripheral lymphoid organs. It stimulates nearby naïve B cells to upregulate CCR7, the chemokine receptor for the chemokines which are present in the paracortical T cell zone. Thus, naïve B cells migrate towards the T cell zone in the peripheral lymphoid organs. This molecules is a:

A Cytokine because it is made by many cell types, produced in response to a specific-stimulus and acts in a paracrine manner.

B Cytokine because it is made by many cell types, produced in response to a specific-stimulus and acts in an autocrine manner.

C Chemokine because it is a cytokine that attracts naïve B cells to a particular site (i.e. paracortical T cell zone)

D Chemokine because it is a cytokine that utilises a concentration gradient to direct naïve B cells to a particular site (i.e. paracortical T cell zone)

E Hormone because it is produced in response to a specific-stimulus and acts in an endocrine manner.

Answer 16

A

M1; 16

Question 17

Which of the following is an example of sterile inflammation?

A Ischaemia reperfusion injury

B Septic shock

C Necrotising fasciitis

D Tuberculosis

E Abscess

Answer 17

A

M1; 17

Question 18

Pattern Recognition Receptors (PRR) regulate inflammation through recognition of Pathogen Associated Molecular Patterns (PAMPS) and Damage Associated Molecular Patterns (DAMPS). Which of the following situations is an example of PAMP recognition?

A Leukocytes producing pro-inflammatory cytokines.

B B cells undergoing isotype switching.

C T cells recognising viral peptides presented by MHC molecules on dendritic cells.

D Antibodies produced by B cells recognising bacterial proteins.

E Phagocytes recognising lipopolysaccharide (LPS) molecules.

Answer 18

E

M1; 18

Question 19

Pattern Recognition Receptors (PRR) regulates inflammation through recognition of Pathogen Associated Molecular Patterns (PAMPS) and Damage Associated Molecular Patterns (DAMPS). Which of the following situations is an example of DAMP recognition?

A Immune cells recognising parenchymal cells undergoing homeostatic apoptosis.

B Adrenaline released during ‘flight or fight’ response.

C Phagocytes recognising the nuclear protein HMGB1 released from dying cells.

D Phagocytes forming granulomas as a result of Mycobacterium tuberculosis infection.

E Cytotoxic T cells killing melanoma cells.

Answer 19

C

M1; 19

Question 20

Which of the following is NOT a Pattern Recognition Receptor [PRR]?

A Toll-like Receptor (TLR)

B NOD-like Receptor (NLR)

C B Cell Receptor (BCR)

D C-type Lectin Receptor (CLR)

E Rig-I like helicase (RLH)

Answer 20

C

M1; 20

Question 21

A 14 year old boy was diagnosed with acute appendicitis and had his appendix removed. The appendix showed oedema, general hyperaemia and engorged vessels. The oedema is most likely the result of:

A increased local metabolic rate

B increased local blood flow

C increased vascular permeability

D formation of pus

E increased collagen deposition by fibroblasts

Answer 21

C

M2; 1

Question 22

A 30 year old patient presented with a swollen lesion on her right thigh. Based on microscopic examination of the lesion, the patient was diagnosed with chronic skin abscess. What would you expect the microscopic examination of the abscess to show?

A Granulomas

B Heavy neutrophil infiltrate

C Heavy collagen deposition

D Palisading epithelioid cells

E Squamous cell carcinoma

Answer 22

B

M2; 2

Question 23

Which of the followings is an example of acute inflammation?

A Foreign body granuloma

B Chronic skin abscess

C Acute Myeloid Leukaemia

D Peritoneal tuberculosis

E Infected ingrown toenail

Answer 23

E

M2; 3

Question 24

A 64 year old patient presented with a diabetic foot ulcer. A negative-pressure wound therapy dressing was applied for 7 days and a biopsy of the healing wound was taken. On microscopic examination, you find newly formed tissue with infiltrating microphages, ingrowth of new vessels and fibroblasts migrating in from periphery. Which of the following best describes this process?

A Granulation

B Regeneration

C Scarring

D Granuloma

E Liquefactive necrosis

Answer 24

A

M2; 4

Question 25

Which of the following process is NOT correct about formation of granulomas? A Foreign particles or pathogens can initiate formation of granulomas. B Phagocytes ingest the inciting agent and releases cytokines to recruit fibroblasts. C Recruitment of circulating monocytes is required; these cells then differentiate into macrophages. D Epithelioid cells fuse to form giant cells. E Fibroblasts are recruited and fibrous tissue forms.

Answer 25

B M2; 5

Question 26

Which of the following is an example of chronic inflammation? A Septic shock B Acute pancreatitis C Chronic Obstructive Pulmonary Disease D Sarcoidosis E Ischaemia reperfusion injury

Answer 26

D M2; 6

Question 27

Coagulation is important in achieving haemostasis. A patient presents with a bleeding wound. After a while, the bleeding stops and haemostasis is achieved. Which of the following processes is NOT required to achieve haemostasis? A Exposure of Tissue Factor B Platelet adhesion to the vessel injury site C Vessel spasm D Triggering of thrombosis by activated monocytes. E Generation of thrombin by Tissue Factor

Answer 27

D M2; 7

Question 28

How does haemostasis initiate inflammation? A Platelets secret chemokines and cytokines to initiate inflammation. B Pathogen associated molecular patterns activate the innate immune system. C Vessel spasm triggers tissue resident leukocytes to migrate to the site of injury. D Exposure to tissue factor cause platelets to adhere and fibrin strands to form. E The sudden change in local blood pressure increases vascular permeability.

Answer 28

A M2; 8

Question 29

The accumulation of multiple thrombi in the circulation in severe infection is called disseminated intravascular coagulation (DIC). How does excessive inflammation cause thrombosis? A Activated monocytes release microparticles expressing Tissue Factor into the circulation. B Extravasation of fluid from the circulation increases blood viscosity. C Platelets secret anti-inflammatory cytokines. D Excessive inflammation increases tissue factor expression on endothelial cells. E Proinflammatory cytokines increase anticoagulant activity.

Answer 29

A M2; 9

Question 30

Extracellular traps consist of strings of DNA and granule proteins to entrap the pathogens and limit infection. Recently their role in triggering thrombosis has been elucidated. Which cell types produce extracellular traps? A Monocytes B Neutrophils C Platelets D Lymphocytes E Red blood cells

Answer 30

B M2, 10

Question 31

Which of the following is a crucial first step of the inciting the sterile injury pathway in acute pancreatitis? A Lipopolysaccharide (LPS) binding to toll like receptor 4 (TLR4) B High-mobility group box protein 1 (HMGB1) binding to toll like receptor 4 (TLR4) on pancreatic acinar cells C High-mobility group box protein 1 (HMGB1) binding to toll like receptor 4 (TLR4) on tissue macrophages D Extracellular double-stranded DNA binding to TOLL-like receptor 4 (TLR4) E Amylase released from damaged acinar cells

Answer 31

C M2; 11 LPS binds to TLR4 but it's a bacterial component - so not sterile HMGB1 is a DAMP TLR4 is expressed on pancreatic ductal cells, endothelial cells and tissue macrophages but NOT acinar cells Mitochondrial DNA activates TLR9 not TLR4

Question 32

Which of the following forms the second signal in the danger associated molecular patterns (DAMP) sensing cell during the sterile injury pathway of acute pancreatitis? A Binding of HMGB1 to P2X7 membrane receptor B Extra-cellular ATP binding to P2X7 receptor on tissue macrophage C Intra-cellular ATP binding to P2X7 receptor on tissue macrophage D Binding of LPS to P2X7 on tissue macrophage E Binding of DS DNA to P2X7 on tissue macrophage

Answer 32

B M2; 12

Question 33

What is the consequence of the activation of P2X7 in the DAMP sensing cell in the sterile injury pathway of acute pancreatitis? A Deceased expression of pro-interleukin-1β (pro-IL-1β ) B Proteolytic maturation of caspase 1 C Inhibition of caspase 1 matuation D Reduced expression of IL-1β E Increased expression of IL-4

Answer 33

B M2; 13

Question 34

Which of the following is an important effector cytokine in the innate immune responses to sterile injury in acute pancreatitis? A IL-1β B IL-4 C IL-10 D IL-13 E TGF- β

Answer 34

A M2; 14

Question 35

Which of the following may be an important mediator of hypotension in this scenario? A A marked decrease in the response to endothelin and angiotensin II B A reduction in serum ionized calcium C Reduced circulating levels of adrenocortical hormones D Reduced levels of Substance P (SP) and calcitonin gene-related peptide (CGRP) released from neurone innervating the pancreas E A marked increase in the response to endothelin

Answer 35

A M2; 15 Marked decrease in the response to endogenous vasoconstrictor substances like endothelin, angiotensin II occurs in severe AP. Both endothelin levels and angiotensin II increase Substance P and CGRP release is increased - and seem to be responsible for neurogenic features of inflammation. Can interact with endothelial cells, mast cells and other immune cells to cause vasodilation and inflammation etc.

Question 36

The main mediator of pyrexia in this scenario is likely: A production of prostaglandin E2 (PGE2) in the pancreas B the systemic release of IL-10 from macrophages in the pancreas C the systemic release of IL-1 from macrophages in the pancreas D the release of IL-1 in the hypothalamus E IL-1 crosses the blood brain barrier and cause the release of Prostaglandin E2

Answer 36

C M2; 16

Question 37

A 46 Year old woman admitted to hospital to delirium and hypotension with a high grade fever. She had diabetes and had recently recovered from shingles of the L2 dermatome. Her investigations show a WCC 1.8, Creatinine 270, INR 1.9 and platelet count 67. She is taken to the operating theatre and the excised tissue is sent for culture. The culture returns a pure growth of Group A Streptoccocus. In this context secreted streptococcal cysteine protease B (SpeB) mediates: A Cleavage of granulocyte chemotactic protein 2 B Inhibition of host neutrophils by binding to their surface CD16 molecules C Degradation of extracellular bacterial DNA D Cleavage of host immunologic mediators such as pre-IL-1β E Conversion of unbound plasminogen molecules into plasmin

Answer 37

D M2; 17

Question 38

Engagement of a streptococcal super-antigen: A requires a second signal mediated by Toll-like Receptor 4 B can result in activation of one quarter of the host’s T cells C occurs at a specific Vβ region of the host’s T cells. D results in potent release of IL-2 and INF-γ from hosts antigen presenting cells E is blocked by bacterial endotoxin

Answer 38

B M2; 18

Question 39

35 year old female presented with a 1 month history of bloody diarrhoea and central abdominal pain. She was stabilised and a flexible sigmoidoscopy performed. This showed continuous inflammation from the rectum to the limit of the scope. The biopsies show neutrophils infiltrating crypt epithelium, collections of neutrophils within crypt and infiltration of surface epithelium with mucosal ulceration. She is given IV hydrocortisone and Infliximab as part of her treatment. Hydrocortisone has the following effects on the inflammatory process in UC: A activation of nuclear factor κB B inhibition of transforming growth factor-β3 (TGF-β) and IL-10 production C up-regulation of IL-8 D differentiation of infiltrating monocytes into a regulatory M2 phenotype E augmentation of T cell proliferation

Answer 39

D M2; 19

Question 40

Which of the following is true of Infliximab? A It activates intracellular signaling nuclear factor kappa B (NF-kB) B Infliximab blocks the engagement of the membrane-bound TNF on T cells with TNF receptor type 2 (TNFRII) on monocytes C The differentiation into M2-like alternative or wound-healing macrophage phenotype is independent of the presence of the Fc portion of infliximab D The inhibition of the binding of membrane-bound TNF expressed on monocytes and the TNFRII expressed on CD4+ T cells, depends on the Fc portion of infliximab. E Soluble TNF targets TNF receptor type 1 on effector cells.

Answer 40

E M2; 20

Question 41

There are many changes in cellular physiology that underlie the malignant phenotype. Which of the following is a hallmark of cancer? A Resistance to apoptosis B Failure to promote angiogenesis C Genomic stability D Increased susceptibility to immune destruction E Finite replicative capability

Answer 41

A M3; 1

Question 42

Tumour suppressor genes encode products which apply brakes to cell proliferation. If these genes or their products are inactivated, cell proliferation may increase, predisposing cells to oncogenesis. Which of the following is encoded by a tumour suppressor gene? A Telomerase B p53 C abl-bcr chimera D EGF receptor E c-myc

Answer 42

B M3; 2

Question 43

Tumours evade or suppress the immune system to persist. Which of the following findings would result in a better prognosis for cancer patients? A Infiltration of tumour by Treg cells. B Accumulation of MDSCs in the tumour microenvironment. C Infiltration of tumour by CD8+ T cells. D Tumour cells expressing a high level of immunomodulatory molecules. E Tumour cells which are resistant to apoptosis.

Answer 43

C M3; 3

Question 44

Under pressure from the immune system, tumours evolve and adapt. How do tumours evolve and adapt to overcome the immune system? A Non-immunogenic tumour cells survive and proliferate. B Tumour cells decrease surface expression of PD-L1 molecules. C Tumour cells produce higher levels of tumour-specific antigens. D Tumour cells increase cell surface expression of MHC-I molecules. E Tumour cells augment antigen processing and presentation pathways.

Answer 44

A M3; 4

Question 45

Tumour cells secrete exosomes containing immunosuppressive molecules and tumour associated antigens. The exosome cargoes also carry tumour derived lipids, mRNA, microRNA and genomic DNA. How do these tumour derived exosomes (TEX) promote downregulation of anti-tumour immunity? A TEX transform normal cells into a malignant cell type. B TEX activate immune cells to secrete pro-inflammatory molecules. C TEX promote tumour-reactive CD8+ T cell expansion. D TEX directly inhibit activation of NK cells and T cells. E TEX increase TLR4 and MHC-II expression on dendritic cells.

Answer 45

D M3;5

Question 46

Anti-PD-1 and anti-CTLA-4 therapies are effective treatment options for some cancer patients. Which of the following options best describes these immunotherapies? A Cancer vaccine B CAR-T cell therapy C Protein kinase inhibitor D Adjuvant immunotherapy E Checkpoint inhibitor

Answer 46

E M3; 6

Question 47

In melanoma patients, which of the following findings would indicate a better response rate to anti-PD-1 therapies? A Increased PD-L1 expression by melanoma cells. B Increased PD-L1 expression by dendritic cells in the draining lymph node. C Increased CTLA-4 expression by infiltrating CD8+ T cells. D Increased CD80 expression by melanoma cells. E Decreased number of infiltrating CD8+ T cells.

Answer 47

A M3; 7

Question 48

Many biomarkers are available to predict response of patients to anti-PD1 therapy. Which of these is NOT an accurate biomarker for predicting response of patients to anti-PD1 therapy? A PD-L1 expression determined by immunohistochemistry B Tumour gene expression profile C High neoantigen load D Tumour infiltrating lymphocyte profile E CRP level

Answer 48

E M3; 8

Question 49

Cancer vaccines are used to help the immune system fight off cancer. Sipuleucel-T is the first FDA approved therapeutic cancer vaccine for prostate cancer. Dendritic cells are extracted from the patient’s white blood cells and incubated with a fusion protein consisting of two parts: PAP [prostate cancer antigen] and GM-CSF [an immune cytokine that helps the APCs to mature]. The activated blood product is reinfused back into the patient. Before being reinfused back into the patient, what are dendritic cells doing during the incubation period? A Dendritic cells are being educated to directly recognise the prostate cancer antigen PAP. B Dendritic cells differentiate into cytotoxic T cells capable of directly killing cancer cells. C Dendritic cells proliferate and expand. D Dendritic cells internally process the fusion protein and present the antigen on the surface via MHC molecules. E Dendritic cells undergo apoptosis and release DAMPS.

Answer 49

D M3; 9

Question 50

Cancer vaccines are used to help the immune system fight off cancer. Sipuleucel-T is the first FDA approved therapeutic cancer vaccine for prostate cancer. Dendritic cells are extracted from the patient’s white blood cells and incubated with a fusion protein consisting of two parts: PAP [prostate cancer antigen] and GM-CSF [an immune cytokine that helps the APCs to mature]. The activated blood product is reinfused back into the patient. Once the activated blood product is reinfused back into the patient, what is the main role of the dendritic cells? A Dendritic cells migrate to the site of cancer and directly kill cancer cells. B Dendritic cells migrate to the site of cancer and modify the tumour microenvironment. C Dendritic cells displaying the antigen on the surface, activate T cells against the cancer antigen. D Dendritic cells secrete GM-CSF. E DAMPs released by dendritic cells activate the immune system.

Answer 50

C M3; 10

Question 51

Cancer vaccines are used to help the immune system fight off cancer. Sipuleucel-T is the first FDA approved therapeutic cancer vaccine for prostate cancer. Dendritic cells are extracted from the patient’s white blood cells and incubated with a fusion protein consisting of two parts: PAP [prostate cancer antigen] and GM-CSF [an immune cytokine that helps the APCs to mature]. The activated blood product is reinfused back into the patient. Regard to the source material, what kind of cancer vaccine is this? A Autologous B Allogeneic C Syngeneic D Xenogeneic E Semi-allogeneic

Answer 51

A M3; 11

Question 52

What does tumour mutation burden correlate with? A Neoantigens B Checkpoint expression level C Response to cancer vaccines D Drug induced toxicity E Genetic stability

Answer 52

A M3; 12

Question 53

Chimeric Antigen Receptors (CARs) are fusion proteins which allows genetically modified CAR-expressing T cells to target cells expressing a specific protein. Which are the two main components that make up this fusion protein? A Constant region of monoclonal antibody & T cell activating component of TCR B Constant region of monoclonal antibody & Hypervariable region of TCR C Constant region of monoclonal antibody & The entire TCR receptor D Variable region of monoclonal antibody & T cell activating component of TCR E Variable region of monoclonal antibody & Hypervariable region of TCR

Answer 53

D M3; 13

Question 54

A patient has recently received CAR-T cell therapy for her B-cell malignancy. She presents with a fever, hypotension and hypoxia. Cytokine Release Syndrome (CRS) occurs in the majority of patients receiving CAR-T cells. How does infusion of CAR-T cells lead to CRS? A CAR-T cells are generated using viral vectors. The viral antigens from genetically engineered CAR-T cells activate other immune cells to release cytokines. B Lysis of large numbers of cancer cells results in metabolic abnormalities and this activates immune cells to release cytokines. C CAR-T cells are genetically engineered to release an enormous amount of cytokines in order to kill cancer cells. Most of cytokines responsible for CRS comes from activated CAR-T cells. D These patients are more susceptible to viral infections because CAR-T cells are unable to kill virally infected cells. Uncontrolled viral infection activates other immune cells to release cytokines. E Upon recognising their target cells, CAR-T cells release inflammatory cytokines, which in turn activates other immune cells to release more inflammatory cytokines.

Answer 54

E M3; 14

Question 55

Which of the following is true about CAR-T cell therapy for cancer patients? A Consistent in quality and characteristics of genetically engineered T cells. B Minimal side-effects. C Not very expensive to generate. D Produce poor responses in B cell malignancies. E Difficult extending this technology to solid tumours.

Answer 55

E M3; 15

Question 56

Neoplastic transformation of a cell results from non-lethal cumulative genetic damage. The genetic change damage may be a consequence of inherited mutations (germline) or acquired mutations (somatic). In these following examples of neoplastic transformation, which of the following genes is responsible? - Chronic Myeloid Leukaemia - Familiar adenomatous polyposis - Familiar breast cancer ``` Options: abl-bcr (Philadelphia chromosome) Rb Cyclins and Cyclin-dependent kinases (CDKs) BRCA1 c-myc p53 APC HPV-16 & -18 Telomerase ```

Answer 56

CML - Philadelphia chromosome FAP - APC Familial breast cancer - BRCA1 M3; 16

Question 57

CD19-targeted CAR-T cell therapy is promising treatment for haematologic malignancies. Recently, scientists have tried repurposing this established therapy for treating non-malignant diseases. Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems. Formation and deposition of autoantibodies produced from hyperactive B cells are thought to be a cause. In murine SLE models, scientists have ablated production of autoantibodies and improved survival by transferring CD19-targeted CAR-T cells into SLE-prone mice. Match the appropriate mechanism to the following experimental observations: - Abrogation of autoantibody production and deposition - Mice are febrile and hypotensive a few days after treatment Options Circulating autoantibodies are targeted by CAR-T cells and destroyed Cytokine release syndrome (CRS) CAR-T cells target cells that exhibit malignant phenotype B cells are destroyed by CAR T cells Hyperactive B cells receive “help” from CAR-T cells to undergo isotype-switching Immune effector cell associated neurotoxicity syndrome (ICANS) Tumour lysis syndrome

Answer 57

Abrogation of autoantibody production and deposition = B cells destroyed by CAR T cells Mice are febrile and hypotensive a few days after treatment = CRS M3; 17

Question 58

Despite the development of more potent immunosuppressive drugs, long-term graft survival has remained relatively static over the past 20 years. Chronic rejection is an important barrier to overcome in order to improve long-term graft function. Which of the following statements is true about chronic rejection? A Chronic rejection is primarily an antibody-mediated response B Complement-fixing alloantibodies are central to the pathogenesis of chronic rejection C Blood vessels are not targeted in chronic rejection D Autoantibodies play a role in acute but not chronic rejection E CD4+ T cells producing cytokines such as TGF-beta are contribute to interstitial fibrosis and vascular smooth muscle hyperplasia in chronic rejection

Answer 58

E M4; 1

Question 59

Acute antibody-mediated rejection (AAMR) can occur at any time after transplantation, and in renal transplantation, AAMR is manifested by a rapid rise in serum creatinine. Which of the following statements is true about AAMR: A AAMR patients respond well to therapy with steroids or T cell-specific reagents B Diagnosis requires detection of MHC (HLA-specific antibodies C Duplication of the glomerular basement membrane is a pathological hallmark D Complement component 4d is deposited in peritubular capillaries E In experimental studies, AAMR cannot be passively transferred using serum from immunised animals

Answer 59

D M4; 2

Question 60

Sir Peter Medawar grafted mice (strain B) with skin grafts from donor mice (strain A). The recipient mice rejected the grafts with a median survival time of 10 days. These sensitised mice were transplanted again with skin grafts from donor mice (strain A) and the recipients rejected the grafts by day 3. What does this experiment demonstrate? A Immunological memory B Cross-reactivity C Passenger leukocyte migration D Formation of donor-specific antibodies E An innate immune response

Answer 60

A M4; 3

Question 61

Which of the following factors is not generally considered when making a decision to accept a potential deceased donor organ offer for a specific kidney transplant recipient? A Donor ABO blood group B Recipient donor specific antibodies C Australian KDRI D The degree of HLA mismatch E Donor proteinuria

Answer 61

A M4; 4

Question 62

Which of the following is not a pre-transplant risk biomarker in current clinical use? A Extent of HLA mismatch B Pre-transplant donor specific antibodies (DSA) C De Novo DSA D Cell-based cross match E Recipient panel reactive antibodies

Answer 62

C M4; 5

Question 63

Which of the following is not a non-invasive diagnostic biomarker used in routine clinical practice currently? A Transplant renal artery resistive indices on duplex ultrasound of the graft B Urinary albumin/creatinine ratio C Urinary BK virus PCR D Renal allograft biopsy E Serum BK virus PCR

Answer 63

D M4; 6

Question 64

In clinical cases of acute rejection following transplantation: A both T cell mediated, and antibody mediated rejection rarely co-exist B the acute rejection can only occur in the days to weeks following transplantation C acute antibody mediated rejection is characterised on histological examination of kidney allografts by infiltrates of lymphocytes and macrophages D immunohistochemical identification of the C4d complement fragment in capillaries of renal allografts is used clinically as an indicator of antibody mediated rejection E acute rejection is rarely seen with current immunosuppressive regimens

Answer 64

D M4; 7

Question 65

Which of the following statements regarding renal allograft dysfunction is TRUE: A Recurrence of glomerular disease is the most common cause of long-term graft loss B Acute allograft dysfunction necessitates renal biopsy C Asymptomatic BK viraemia may progress to nephropathy D Progressive decline in graft function is rarely secondary to non-immune recipient factors E Graft survival following re-transplantation is equivalent to primary transplants

Answer 65

C M4; 8

Question 66

The precursor frequency of alloreactive T cells is very high. It is estimated that up to 10% of T cells can directly recognise a set of major histocompatibility complex (MHC/HLA) alloantigens, a proportion that is 100- to 1000-fold greater than that observed after infection. There are two hypotheses. The “High determinant density” hypothesis states that T cells recognise polymorphic regions of MHC independently of peptides and the “multiple binary complexes” hypothesis states that T cells recognise many possible complexes between allo-MHC and self-peptides. Which of the following experimental findings would most strongly support the “multiple binary complexes” hypothesis? A All alloreactive T cells have the same TCR sequence B Within each individual, there is a polyclonal population of alloreactive T cells C Alloreactive T cells recognise targets which are tissue-specific D Alloreactive T cells can also be autoreactive E Alloreactive T cells can recognise viral peptides presented by self-MHC

Answer 66

C M4; 9

Question 67

The most accurate predictor of graft loss at 5 years is: A non-glomerulonephritis cause of renal disease B a doubling of serum creatinine C biopsy showing tubular atrophy and interstitial fibrosis at 3 years D a 30% decline in GFR between 1-3 years post-transplant E biopsy proven acute rejection at 3 months

Answer 67

D M4; 10

Question 68

With respect to interpretation of cell-based cross matches pre-transplant, which of the following statements is most appropriate if there is a positive B cell cross match and negative T cell cross match? A There are no (or only very low titre) donor-specific antibodies in the potential recipient serum B Multiple class I and class II DSA are likely present C Multiple DSA to class I are likely present D There are likely class II DSA present in high titre E There is likely a technical issue with the assay

Answer 68

E M4; 11

Question 69

The immunosuppression regimen in Australia and New Zealand for a recipient of a deceased donor kidney transplant assessed as low immunological risk would include the following EXCEPT? A Tacrolimus B Ciclosporin C Basiliximab D Anti-thymocyte Globulin E Mycophenolate mofetil

Answer 69

D M4; 12

Question 70

Which of the following regimens has the lowest risk of associated CMV infection in kidney transplant recipients? A Low dose ciclosporin B Standard dose ciclosporin C Standard dose tacrolimus D Low dose tacrolimus E Sirolimus

Answer 70

Answers say D Lecture says low dose sirolimus is the lowest (no mention of normal dose sirolimus) M4; 13

Question 71

A: Activation of alloreactive T cells is a multi-step process that ultimately leads to graft rejection. Donor dendritic cells (DC) migrate out of a vascularised graft soon after surgery to the host’s secondary lymphoid organs and activate alloreactive T cells. B: Donor DCs have a limited life span and are recognised as non-self and destroyed by the host immune system. Intact donor MHC molecules from are transferred donor cells to host DCs and these “cross-dressed” host DCs continue to activate CD8+ T cells. C: Some donor antigens are processed into peptides by host DCs and these allopeptides are presented by self-MHC molecules to T cells. D: Activated alloreactive T cells migrate into the donor graft and mediate graft rejection. Match the appropriate mechanism to the following processes: Direct allorecognition Indirect allorecognition Semi-direct allorecognition Minor antigen recognition

Answer 71

A Direct allorecognition B Semi direct allorecognition C Indirect allorecognition D Direct allorecognition M4; 14

Question 72

A 43 year old male recipient with IgA nephropathy confirmed on biopsy 5 years previously received an offer for a deceased donor kidney transplant after 6 months of peritoneal dialysis. He was blood group AB. The donor offer was for a kidney from a 50-year-old donation after cardiac death, blood group AB. There was a 6/6 HLA mismatch. B and T cell cross match was negative. There were two DSA to CW4 (MFI 1612) and to DQAA1 (MFI 956). The transplant was performed with a first warm iscahemic time of 38 minutes, cold ischaemic time of 598 minutes and a second warm ischaemic time of 23 minutes. Which of the following factors represents the great risk for rejection in the recipient? A Cold Ischaemic time of 598 minutes B The 6/6 HLA mismatch C Second warm Ischaemic time of 23 minutes D Kidney disease being IgA nephropathy E Donor age of 50

Answer 72

B M4; 15

Question 73

A 43 year old male recipient with IgA nephropathy confirmed on biopsy 5 years previously received an offer for a deceased donor kidney transplant after 6 months of peritoneal dialysis. He was blood group AB. The donor offer was for a kidney from a 50-year-old donation after cardiac death, blood group AB. There was a 6/6 HLA mismatch. B and T cell cross match was negative. There were two DSA to CW4 (MFI 1612) and to DQAA1 (MFI 956). The transplant was performed with a first warm iscahemic time of 38 minutes, cold ischaemic time of 598 minutes and a second warm ischaemic time of 23 minutes. If this offer were accepted, which of the following treatments prior to transplant might provide the greatest protection from antibody-mediated rejection? A Induction immunosuppression with methylprednisolone B Use of hypothermic machine perfusion C Immunoabsortion column to remove anti-A antibodies D Immunoabsortion column to remove anti-B antibodies E Plasmapharesis

Answer 73

E M4; 16

Question 74

A 43 year old male recipient with IgA nephropathy confirmed on biopsy 5 years previously received an offer for a deceased donor kidney transplant after 6 months of peritoneal dialysis. He was blood group AB. The donor offer was for a kidney from a 50-year-old donation after cardiac death, blood group AB. There was a 6/6 HLA mismatch. B and T cell cross match was negative. There were two DSA to CW4 (MFI 1612) and to DQAA1 (MFI 956). The transplant was performed with a first warm iscahemic time of 38 minutes, cold ischaemic time of 598 minutes and a second warm ischaemic time of 23 minutes. Which of the following factors in the donor is not required to calculate the Australian KDRI? A Height B Weight C Proteinuria D Treated hypertension E Diabetes

Answer 74

C M4; 17

Question 75

Which of the following kidney donors would be considered an expanded criteria donor (ECD)? A A donor after circulatory death with a first warm ischaemic time (from withdrawal of life support to cessation of circulation) of 61 minutes B Deceased donor with an estimated risk of graft failure that is > or = 70% compared to deceased donor kidneys with standard characteristics of transplant suitability C A deceased donor with type I diabetes D Living donor over age 60 E A deceased donor with a post-procurement frozen section biopsy showing acute tubular necrosis

Answer 75

B M5; 1

Question 76

Compared to kidneys from donation after brain death, organs from donation after circulatory death have: A Equivalent long-term graft survival B An equivalent rate of discard C Higher rate of initial graft function D Are considered ECD E Equivalent risks of delayed graft function

Answer 76

A M5; 2

Question 77

A 52-year-old man is transferred to intensive care following a collision in a motorcycle accident. He has a severe head injury and is deeply unconscious without sedation, but is breathing spontaneously when ventilation is paused to conduct brain death testing. Following a discussion of the prognosis and outcomes with his family by the intensive care team, it is decided that continued life support would not be in accordance with his wishes, given the degree of injury. If he were referred as a donor and the DCD pathway were followed, what type of DCD would this situation most likely represent according to the modified Maastricht classification for donors after circulatory death (Detry, 2012)? A Category I B Category II C Category IVB D Category IVA E Category III

Answer 77

E M5; 3

Question 78

A 52-year-old man is transferred to intensive care following a collision in a motorcycle accident. He has a severe head injury and is deeply unconscious without sedation, but is breathing spontaneously when ventilation is paused to conduct brain death testing. Following a discussion of the prognosis and outcomes with his family by the intensive care team, it is decided that continued life support would not be in accordance with his wishes, given the degree of injury. In the case described above, the DCD pathway was followed. Withdrawal of life support was at 06:32. Cessation of circulation occurred at 06:52. The skin incision was made at 06: 59. The in situ cold perfusion commenced at 07:02. The organs were removed and placed in ice slush at 07:45. The organs were removed from the ice and placed in the recipient at 15:45. Reperfusion was at 16:07. The first warm ischaemic time is: A 30 minutes B 20 minutes C 7 minutes D 480 minutes E 22 minutes

Answer 78

A M5; 4

Question 79

A 52-year-old man is transferred to intensive care following a collision in a motorcycle accident. He has a severe head injury and is deeply unconscious without sedation, but is breathing spontaneously when ventilation is paused to conduct brain death testing. Following a discussion of the prognosis and outcomes with his family by the intensive care team, it is decided that continued life support would not be in accordance with his wishes, given the degree of injury. In the case described above, the DCD pathway was followed. Withdrawal of life support was at 06:32. Cessation of circulation occurred at 06:52. The skin incision was made at 06: 59. The in situ cold perfusion commenced at 07:02. The organs were removed and placed in ice slush at 07:45. The organs were removed from the ice and placed in the recipient at 15:45. Reperfusion was at 16:07. The second warm ischaemic time is: A 20 minutes B 480 minutes C 7 minutes D 22 minutes E 30 minutes

Answer 79

D M5; 5

Question 80

Which of the following factors, if observed, would preclude the diagnosis of brain death? A Normothermia B Nuclear medicine brain scan showing absence of cerebral perfusion C Normal CT of the brain D Serum glucose of 5.7mmol/L E Toxicology screen negative for opiates

Answer 80

C M5; 6

Question 81

Which of the following, released from cells in organs procured following prolonged cold ischaemia in transport from a deceased donor, does not signal through Toll-Like Receptor 4? A DNA B HMGB1 C HSP 70 D Hyaluronic acid E Heparan Sulphate

Answer 81

A M5; 7

Question 82

With respect to in situ perfusion techniques in liver retrieval from deceased donors, which of the following is correct? A Dual perfusion is associated with superior graft survival of grafts from higher risks donors as defined by age >60 years, cause of death unrelated to CVA, trauma, and/or anoxia and/or with a prolonged cold ischaemic time (≥12 hours). B Dual perfusion is associated with a higher rate of recipient portal vein thrombosis C Dual (portal and aortic) perfusion is associated with superior overall graft survival D Aortic only perfusion is a higher rate of recipient hepatic artery thrombosis E Dual perfusion is associated with a lower rate of biliary complications in the recipient

Answer 82

A M5; 8

Question 83

The systemic response to brain death includes all of the following except? A Increase in IL-1 B Increased serum cortisol C Increase in TNF D Increased leucocyte infiltration of organs E Increase in IL-6

Answer 83

B M5; 9

Question 84

With respect to the kidney-only brain dead donor management all of the following are recommended with the exception of? A Maintaining enteral nutrition B Low tidal volume ventilation C Hormonal resuscitation D Maintaining normothermia E Preventing hypernatreamia

Answer 84

D M5; 10

Question 85

Matzinger’s “danger hypothesis” states that the immune system does not discriminate between self and non-self, but rather distinguishes between “damaged” and “normal”. She suggested that danger signals from distressed cells potentiate a productive immune response. Which of the following experimental findings most strongly support this hypothesis? A Neoplastic cells evade the immune system by downregulating the expression of neoantigens. B Allogeneic grafts are rejected but syngeneic grafts are accepted. C Cells undergoing apoptosis can still produce an immune response. D In vitro, Neoplastic cells that release DAMPs are eliminated but those that do not are spared. E Cells infected with a virus can trigger an immune response.

Answer 85

D M5; 11

Question 86

Which of the following options is NOT a “danger signal”? A Lipopolysaccharide B Double stranded RNA C Heat-shock protein D Donor MHC class II E HMGB1

Answer 86

D M5; 12

Question 87

What is the main adaptor molecule involved in the TLR intracellular signalling pathway? A MyD88 B NF-kB C IRF3 D TRIF E CD3

Answer 87

A M5; 13

Question 88

Which of the following is the consequence of TLR signalling on immature antigen presenting cells (APCs)? A Upregulation of CD40 B Retention at the site of injury C Upregulation of co-inhibitory molecules (such as PD-1) D Secretion of tolerogenic cytokines E Downregulation of MHC molecules

Answer 88

A M5; 14

Question 89

Which feature of the complement cascade is directly responsible for cell lysis in damaged organs? A Formation of the C3 convertase B C5a recruitment of neutrophils C C4d deposition in capillaries D Formation of the C5-9 complex E Binding of neoantigen-specific antibody to tissues

Answer 89

D M5;15

Question 90

The extracellular matrix (ECM) plays a major role in the progression of ischaemia-reperfusion injury. Which of the following statements is true? A Enzymes that can degrade the ECM, become functional in the acidic environment of inflammation. B Ischaemia decreases the expression of heparan sulphate and hyaluronic acid. C Only intact matrix molecules have immunostimulatory effects. D Matrix degradation prevents infiltration of leukocytes throughout the graft parenchyma. E Most of the clearance of hyaluronic acid metabolites occurs in the spleen.

Answer 90

A M5; 16

Question 91

Mitochondria are particularly susceptible to hypothermic injury and IRI. Swelling/rupture of mitochondria releases apoptotic factors. The following statements describe key steps after tissue ischaemia and before mitochondria swelling/rupture. Place them in the correct order. A Mitochondria are impeded from producing ATP though oxidative phosphorylation, and the ATP produced via glycolysis is broken down. B This contributes to ROS overproduction and eventually mitochondrial permeability transition pore (mPTP) opening. The mitochondrial membrane potential is lost and the electron transfer chain is uncoupled. C Once reperfused and supplied with oxygen, the cell shifts to aerobic metabolism and pH increases, which opens the mPTP and further increases ROS levels. D The cell acidifies because of lactic acid production and the Na+/H+ exchanger attempts to restore cellular pH. Increased sodium gradient drives the Na+/Ca2+ antiporter, leading to an increased intracellular and intramitochondrial Ca2+ concentration.

Answer 91

DBAC M5; 17

Question 92

Which of the following organs is least likely to undergo rejection following allogeneic transplantation? A Kidney B Liver C Heart D Lungs E Pancreas

Answer 92

B M6; 1

Question 93

Donor bone marrow transplantation with non-myeloablative conditioning has been shown to induce renal allograft tolerance in humans. Which of the following processes plays a principal role in tolerance induction? A Anergy B Cytokine modulation C Organ-specific tolerance D Clonal deletion E Co-stimulatory blockade

Answer 93

D M6; 2

Question 94

Donor bone marrow transplantation with non-myeloablative conditioning has been shown to induce renal allograft tolerance in humans. Which of the following is a major complication of haematopoietic chimerism? A Graft rejection B Carcinogenesis C Graft-versus-host disease (GvHD) D Acute kidney injury E Susceptibility to opportunistic infections.

Answer 94

C M6; 3

Question 95

Exposure to viral infection prior to transplant can block tolerance induction. Which of the following statements best explains this? A Viral infection interferes with immunosuppressive drugs B The number of naïve alloreactive T cells increases exiting the thymus increases during viral infection C Alloreactive T cells are primed by exposure to cross-reactive antigens D Viral infection enhances the recirculation of memory T cells from the lymph node E Viral reactivation increases the expression of co-stimulatory molecules

Answer 95

C M6; 4

Question 96

Which of the following patient factors would present a significant barrier to the achievement of transplantation tolerance? A History of an underlying autoimmune disease B Length of time spent on dialysis C The total number of T cells D The patient is a “super-metaboliser” of immunosuppressive drugs E The patient’s T cells bear a mutated receptor making them resistant to the actions of corticosteroids

Answer 96

A M6; 5

Question 97

Which of the following pairs of molecules are ligands for TLR9? A Hyaluronan and HMGB1 B Biglycan and Hyaluronan C Hyaluronan and LPS D HMGB1 and LPS E HMGB1 and CpG DNA

Answer 97

E M6; 6

Question 98

Regarding approaches to achieving operational tolerance, which of the following statements is correct? A Tolerance cannot develop in patients receiving standard immunosuppression B Up to 80% of liver transplant recipients can be weaned from immunosuppression C Immunosuppression weaning is difficult without reliable biomarkers to predict the tolerant state D Tolerance induction strategies have not been trialled in a clinical setting E Operational tolerance is permanent once established

Answer 98

C M6; 7

Question 99

Tolerance allows a donor organ to be accepted by the recipient’s immune system in the absence of continuous immunosuppression. Which of the following statements best describes “anergy”? A T cells are unable to respond to antigens in certain situations B T cells receive insufficient signals and become unresponsive C T cells express tolerogenic cytokines that dampen immune responses D T cells are induced to undergo apoptosis E T cells lose their co-stimulatory molecule expression

Answer 99

B M6; 8

Question 100

Which of the following options is NOT a side effect of chronic use of conventional immunosuppression? A Increased rate of malignancies B Increased susceptibility to opportunistic infections C Promotion of cardiovascular diseases D Metabolic derangement E Chronic antibody-mediated rejection

Answer 100

E M6; 9

Question 101

Controlled withdrawal of immunosuppression in selected groups of liver recipients can reveal operational tolerance. Patients who have achieved tolerance have a much better quality of life and improved graft and patient survival. Which of the following factors best predicts which patient can be weaned from immunosuppression? A Size of the liver graft B The extent of haematopoietic chimerism C Normal levels of Alanine and Aspartate Aminotransferases D A liver biopsy showing no inflammation E Time since transplantation

Answer 101

E M6; 10

Question 102

Which of the following is NOT part of a potential tolerance induction strategy? A Novel checkpoint inhibitor B Development of haematopoietic chimerism C Donor-specific CD4+ CD25+ FoxP3+ Treg therapy D Donor-specific CD8+ Treg therapy E Donor-specific Chimeric Antigen Receptor (CAR) Treg therapy

Answer 102

A M6; 11

Question 103

With respect to regulatory T cell therapy, which of the following statements is true? A Polyclonal Tregs are more effective than donor-specific Tregs B Tregs do not have to recognise all major and minor histocompatibility antigens to be effective C Treg-induced tolerance can only be maintained for the short-term D Donor-specific Treg infusion may lead to GvHD if foxP3 expression is unstable E Treg therapy has not been trialed in a clinical setting

Answer 103

B M6; 12

Question 104

Which of the following are significant limitations to implementation of regulatory T cell therapy? A Finding an HLA-identical donor from whom Tregs can be isolated, is very challenging B Tregs need to be frequently administered C Clinical grade allospecific Tregs cannot be expanded readily in vitro D Tregs are prone to destabilise in strongly inflammatory environments E Tregs can only confer tolerance to MHC-II antigens

Answer 104

D M6; 13

Question 105

Activation of mature T cells requires multiple signals. Which of the following molecules found on antigen presenting cells provides costimulation to T cells? A CD40 B IL-2 C CTLA4 D TCR E CD3

Answer 105

A M6; 14

Question 106

Memory responses are different from primary responses. Which of the following statements is true of memory T cells? A Donor-reactive memory T cells are frequently found in patients awaiting transplant B Central memory T cells are specialised to kill target cells immediately C Memory T cells can only be stimulated by professional APCs D Costimulation is mandatory for the activation of memory T cells E The response of memory T cells to low antigen doses is weak

Answer 106

A M6; 15

Question 107

Indicate whether the following statements are true or false. - Transient donor chimerism is more effective at inducing tolerance than full donor chimerism. - Around 80% of selected patients who have received a liver transplant longer than 10 years prior can be successfully weaned from immunosuppression. - Biomarkers have been able to identify kidney transplant patients suitable for immunosuppression weaning. - Methylation of CpG islands in the TSDR of the foxP3 gene is a marker of Treg stability. - Prevention of recirculation of memory T cells from the lymph node to the graft impedes rejection.

Answer 107

- Transient donor chimerism is more effective at inducing tolerance than full donor chimerism. FALSE - Around 80% of selected patients who have received a liver transplant longer than 10 years prior can be successfully weaned from immunosuppression. TRUE - Biomarkers have been able to identify kidney transplant patients suitable for immunosuppression weaning. FALSE - Methylation of CpG islands in the TSDR of the foxP3 gene is a marker of Treg stability. FALSE - Prevention of recirculation of memory T cells from the lymph node to the graft impedes rejection. TRUE

Question 108

Haemostasis causes inflammation: A. Because the wound is infected B. By vasoconstriction C. By recruiting neutrophils D. By the function of platelet granules

Answer 108

C, D M2 lecs

Question 109

Inflammation causes thrombosis: A. By stimulating the release of tissue factor from neutrophils B. By activating platelets C. Only in infections D. Through humoral immunity

Answer 109

B, D M2 lecs

Question 110

What is a major mechanism for bleeding complications in severe acute pancreatitis? A. A rise in platelet count B. Dilution of coagulation factors by fluid C. Hypocalaemia leading to reduced activity of coagulation factors D. Reduced levels of thrombomodulin from the endothelial cell surface E. Reduced levels of P Selectin on endothelial cells

Answer 110

D is the best response Cascade inhibitors like protein C and S are consumed and inhibited (therefore you clot more) Consumed (makes sense) Inhibited - IL-1 downregulates thrombomodulin on endothelial cell surfaces Normally thrombomodulin activates Protein C and S Less thrombomodulin = less Protein C and S But this should mean the patient will clot more (less anti-thrombotic effects) not bleed more M2 lecs

Question 111

3 weeks after admission with acute necrotizing pancreatitis, a 22 year old man deteriorates. - HR 110bpm, SBP 90mmHg, 38.7 °C respiratory rate 22bpm. - Lab studies a serum Amylase of 45u/l and leucocytosis (WCC 21). - He has gram –ve bacteraemia These systemic clinical manifestations are most likely : A. An example of a primarily adaptive immune response to recurrent autoimmune pancreatic inflammation B. Is independent of the immune system C. Is mediated primarily by a bacterial exotoxin D. An example of a primarily innate immune response E. Is not primarily immune mediated

Answer 111

D Most likely bacterial related, gas forming organisms Bacterial endotoxin not exotoxin M2 lecs

Question 112

The signalling pathway of LPS as a PAMP operates through: A. Direct binding of LPS to TLR4 B. Binding of LPS in a complex with MD2 receptor and TLR4 C. Binding of MyD88 and LPS in a complex with TLR4 D. Is largely independent of TLR4 E. Is mediated by binding of TLR4 to CD14

Answer 112

B M2 lecs

Question 113

What could be the rationale for observation of the necrosis, as opposed to immediate intervention with necrosectomy after drainage? A. There is high quality clinical evidence that delay in necrosectomy reduces the risk of complications and mortality. B. Delayed necrosectomy is recommended in clinical practice guidelines. C. Necrosectomy is always necessary but is easier if performed later D. There is high quality clinical evidence that if necrosectomy is delayed there is less risk of requiring open surgery E. There is high quality clinical evidence that if necrosectomy is delayed there is less risk of requiring blood transfusion

Answer 113

B - there is no high quality evidence M2 lecs

Question 114

What is the benefit of the STEP UP approach (percutaneous drainage + minimally invasive retroperitoneal necrosectomy) in comparison to open necrosectomy for severe necrotising pancreatitis? 4 benefits 2 non-inferior

Answer 114

Less treatment failure, complications, multiorgan failure, new onset DM Similar rates of pancreatic fistula and infected necrosis M2 lecs

Question 115

4. What could be the immunological basis for improved outcomes with the STEP-UP approach? A. The STEP-UP approach reduces damage to tissue and so the release of endogenous DAMP B. The STEP-UP approach reduces release of LPS from infected pancreatic necrosum. C. The minimally invasive retroperitoneal necrosectomy is less likely to produce a pancreatic fistula D. The STEP-UP approach reduces new onset diabetes E. The STEP-UP approach causes more activation of the renin-angiotensin system.

Answer 115

A M2 lecs

Question 116

- 46F admitted to hospital with delirium, hypotension, high grade fever - Hx of diabetes and recently recovered from shingle of the L2 dermatome - WCC 1.8, Cr 270, INR 1.9 and Plts 67 The skin necrosis in this case is due to: A. Is due to bacterial superantigens B. Is independent of the immune system C. Is mediated primarily by bacterial exotoxins D. An example of a primarily adaptive immune response E. Is primarily immune mediated

Answer 116

C - Superantigens may play a role - Innate immune response is involved but not exclusively - Primarily bacterial mediated, not like an autoimmune disease M2 lecs

Question 117

The inflammation in ulcerative colitis is A. Due to bacterial superantigens B. Independent of the immune system C. Independent of the intestinal microbiota D. Due to a dysregulated adaptive response with Th2/9 phenotype E. Due to abnormal lymphocyte trafficking

Answer 117

D | Normal lymphocyte trafficking is part of the disease process

Question 118

With respect to TLR signalling in transplantable organs, which of the following is/are true? A. HMGB1 released from the nucleus is a ligand for TLR4 B. Renal tubular epithelial cells produce chemokines upon TLR4 stimulation C. Selectin and integrin expression on graft endothelial cells increases as a result of TLR engagement. D. TLR4 signaling plays an important role in the pathogenesis of renal IRI.

Answer 118

ABCD M5 lecs

Question 119

Regarding the actions of complement in IRI A. Expression of complement regulatory proteins increases in ischaemic tissues. B. Only the lectin pathway of complement activation plays a role in IRI. C. MBL can bind directly to tissue components exposed as a result of ischemia. D. Phospholipids are neoantigen targets for complement-fixing antibodies.

Answer 119

CD M5 lecs

Question 120

The ECM influences the outcome of ischaemia-reperfusion injury in which of the following ways A. Degradation of the matrix releases sequestered cytokines and chemokines. B. Binding of C1q to decorin and biglycan inhibits the classical pathway of complement activation. C. Matrikines are ligands for TLR4. D. Chondroitin sulphate acts as a DAMP.

Answer 120

AB M5 lecs

Question 121

Consequences of hypothermic storage and reperfusion include A. Mitochondrial shrinkage B. Reduced pH and ATP production because of increased reliance on glycolysis. C. Calcium influx and increased production of reactive oxygen species. D. Release of mitochondrial DNA.

Answer 121

BCD M5 lecs

Question 122

In allograft rejection, which of the following statements is true: A. Hyperacute rejection does not occur in the absence of secondary lymphoid organs. B. lymph vessels are a primary target of all forms of rejection. C. Ischaemia-reperfusion injury potentiates acute and chronic rejection via the release of DAMPs and the engagement of pattern-recognition receptors. D. Intimal hypertrophy and interstitial fibrosis are characteristics of acute rejection.

Answer 122

C M4 lecs

Question 123

Regarding cell-mediated rejection, which of the following statements is/are correct: A. The formation of an immunological synapse is critical for CD8+ T cell killing of target cells. B. Delayed-type hypersensitivity responses primarily involve B cells and macrophages. C. Nude mice do not reject skin grafts. D. Deficiency of Granzyme B alone is sufficient to delay the tempo of graft rejection.

Answer 123

A C M4 lecs

Question 124

Regarding antibodies and complement in graft rejection, which of these statements is correct: A. Only complement-fixing antibodies play a role in the pathogenesis of acute antibody-mediated rejection. B. C4d deposition is a hallmark of antibody-mediated rejection. C. Engagement of complement receptors increases the expression of adhesion molecules on the graft endothelium. D. Polymorphisms of complement C3 influence renal allograft survival and function.

Answer 124

ABCD M4 lecs

Question 125

Regarding allorecognition, which of the following statements is correct: A. Most alloreactive T cells recognize allogeneic MHC molecules irrespective of the bound peptide. B. Indirect allorecognition facilitates CD4 T cell help for alloreactive B cells. C. The precursor frequency of alloreactive T cells is higher than that of cells recognizing conventional antigens. D. The semi-direct pathway of allorecognition promotes continued CD8+ T cell priming after donor DC have disappeared.

Answer 125

BCD M4 lecs

Question 126

Regarding allorecognition, which of the following statements is correct: A. MICA presents endogenous peptides to B cells. B. B cell epitopes need to be in a location on the donor MHC molecule where they are accessible to antibody binding. C. Minor histocompatibility antigens can only be presented by recipient MHC class II molecules. D. NK cells can identify allogeneic cells as foreign due to the absence of self-MHC ligands for NK inhibitory receptors.

Answer 126

B, D M4 lecs

Question 127

Regarding allorecognition, which of the following statements is correct: A. Responses against minor histocompatibility antigens are generally weaker and slower than responses against major antigens. B. A greater number of MHC mismatches is associated with improved graft survival. C. Some single MHC mismatches are well-tolerated while others provoke vigorous anti-donor responses. D. MHC mismatches differ in their likelihood of generating antibody responses.

Answer 127

A C D M4 lecs